Published online Jan 28, 2016. doi: 10.3748/wjg.v22.i4.1449
Peer-review started: May 6, 2015
First decision: August 31, 2015
Revised: September 30, 2015
Accepted: November 30, 2015
Article in press: December 1, 2015
Published online: January 28, 2016
Processing time: 267 Days and 5.6 Hours
Patients infected with the hepatitis C virus (HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer (NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection.
Core tip: Natural killer (NK) cells protect our body from viral infections by killing infected cells and secreting cytokines that inhibit viral replication. Unlike T lymphocytes that require priming by antigen presenting cells, NK cells directly recognize virus-infected cells and immediately exert antiviral effector functions. Researchers who investigate immunity to hepatitis C virus (HCV), therefore, have been interested in NK cells. This review will give readers an overview of reports on NK cells in hepatitis C and insights into the role of NK cells in the defense against HCV infection, the immunopathogenesis of hepatitis C, and the prediction of the treatment response.